4,878 research outputs found
Pacing-induced regional differences in adenosine receptors mRNA expression in a Swine model of dilated cardiomyopathy.
The adenosinergic system is essential in the mediation of intrinsic protection and myocardial resistance to insult; it may be considered a cardioprotective molecule and adenosine receptors (ARs) represent potential therapeutic targets in the setting of heart failure (HF). The aim of the study was to test whether differences exist between mRNA expression of ARs in the anterior left ventricle (LV) wall (pacing site: PS) compared to the infero septal wall (opposite region: OS) in an experimental model of dilated cardiomyopathy. Cardiac tissue was collected from LV PS and OS of adult male minipigs with pacing-induced HF (n = 10) and from a control group (C, n = 4). ARs and TNF-α mRNA expression was measured by Real Time-PCR and the results were normalized with the three most stably expressed genes (GAPDH, HPRT1, TBP). Immunohistochemistry analysis was also performed. After 3 weeks of pacing higher levels of expression for each analyzed AR were observed in PS except for A1R (A1R: C = 0.6±0.2, PS = 0.1±0.04, OS = 0.04±0.01, p<0.0001 C vs. PS and OS respectively; A2AR: C = 1.04±0.59, PS = 2.62±0.79, OS = 2.99±0.79; A2BR: C = 1.2±0.1, PS = 5.59±2.3, OS = 1.59±0.46; A3R: C = 0.76±0.18, PS = 8.40±3.38, OS = 4.40±0.83). Significant contractile impairment and myocardial hypoperfusion were observed at PS after three weeks of pacing as compared to OS. TNF-α mRNA expression resulted similar in PS (6.3±2.4) and in OS (5.9±2.7) although higher than in control group (3.4±1.5). ARs expression was mainly detected in cardiomyocytes. This study provided new information on ARs local changes in the setting of LV dysfunction and on the role of these receptors in relation to pacing-induced abnormalities of myocardial perfusion and contraction. These results suggest a possible therapeutic role of adenosine in patients with HF and dyssynchronous LV contraction
Algorithms for Colourful Simplicial Depth and Medians in the Plane
The colourful simplicial depth of a point x in the plane relative to a
configuration of n points in k colour classes is exactly the number of closed
simplices (triangles) with vertices from 3 different colour classes that
contain x in their convex hull. We consider the problems of efficiently
computing the colourful simplicial depth of a point x, and of finding a point,
called a median, that maximizes colourful simplicial depth.
For computing the colourful simplicial depth of x, our algorithm runs in time
O(n log(n) + k n) in general, and O(kn) if the points are sorted around x. For
finding the colourful median, we get a time of O(n^4). For comparison, the
running times of the best known algorithm for the monochrome version of these
problems are O(n log(n)) in general, improving to O(n) if the points are sorted
around x for monochrome depth, and O(n^4) for finding a monochrome median.Comment: 17 pages, 8 figure
Social setting, intuition, and experience in lab experiments interact to shape cooperative decision-making
Recent studies suggest that cooperative decision-making in one-shot interactions is a history-dependent dynamic process: promoting intuition versus deliberation has typically a positive effect on cooperation (dynamism) among people living in a coop- erative setting and with no previous experience in economic games on cooperation (history-dependence). Here we report on a lab experiment exploring how these findings transfer to a non-cooperative setting. We find two major results: (i) promoting intuition versus deliberation has no effect on cooperative behavior among inexperienced subjects living in a non-cooperative setting; (ii) experienced subjects cooperate more than inexperienced subjects, but only under time pressure. These results suggest that cooperation is a learning process, rather than an instinctive impulse or a self-controlled choice, and that experience operates primarily via the channel of intuition. In doing so, our findings shed further light on the cognitive basis of human cooperative decision-making and provide further support for the recently proposed Social Heuristics Hypothesis
CITRUS TRISTEZA VIRUS RESISTANCE GENE LOCUS: SMALL RNA PROFILE AND PRELIMINARY EPIGENETIC STUDIES
Small interfering RNAs (siRNAs), play a vital role in epigenetics of plant virus-host plant interactions. It has been extensively studied at both the transcriptional and post-transcriptional levels. In plants, siRNAs initiate and manage gene silencing by directing DNA methylation and/or histone methylation. In Arabidopsis, the ~24 nt siRNAs directs DNA methylation (RNA-directed DNA methylation, RdDM) and chromatin remodeling at their target loci. Recent advances in highthroughput sequencing techniques has enabled thorough exploration of small RNAs populations and allow rapid analysis of massive datasets to assemble complete full-length genome sequence for different plant species. This large database of sequence information also allows identification of genome regions specifically matched by siRNAs that likely differ among tolerant, resistant or
susceptible hosts and advance epigenetic studies on diseased plants.
Resistance to Citrus tristeza virus (CTV), the most severe virus affecting Citrus spp.,
associated with a single dominant gene locus Ctv occurring in Poncirus trifoliata while all Citrus spp. are considered susceptible. This locus contains 22 putative genes, but their regulation and mechanism for resistance remains unknown.
In our study, CTV was graft-inoculated on Carrizo citrange (Poncirus trifoliata x C. sinensis
(I think) ) and C. aurantium (sour orange) seedlings, and the population of siRNA characterized by high-throughput sequencing using an ILLUMINA platform. The Ctv-derived siRNA (~2% of the total short reads) were dominated in both hosts by the 24-nt. However, CTV infection caused an increase in accumulation of 24-nt siRNA sequences homologous to the Ctv gene in Carrizo but it decreased in sour orange. Distribution of the 24nt along the Ctv gene locus (282Kb) had a clearly different distribution between the two host. The predominant hot spot of siRNA in Carrizo mapped in the putative gene Ctv-20, whereas in sour orange it associated to the intergenic region between the putative genes Ctv-11 and Ctv-12, where a Copia-like retrotransposon C is located. This distribution profile was conserved for each species between CTV-infected and uninfected plants but, as previously mentioned, the frequency of the 24nt siRNAs was altered by the presence of the virus.
We supposed that the different profile of 24nt between the two host in the locus ctv is due to
RdDM mechanisms. To demonstrate the methylation status of the resistance locus we performed a
bisulfite treatment of DNA. in which unmethylated cytosine was converted to uracile, while
methylated cytosine did not react. A methylcytosines mapping was carried out on Ctv-11 and Ctv-12 sequences. By specific software were found 5 different CpG islands in the Copia-likeretrotransposon sequence and 42 primer pair were designed. The PCR analyses have been carried out using MSP and BSP primers followed by combined bisulfite restriction analysis (COBRA)
Stabilizing the Complex Structure in Heterotic Calabi-Yau Vacua
In this paper, we show that the presence of gauge fields in heterotic
Calabi-Yau compacitifications causes the stabilisation of some, or all, of the
complex structure moduli of the Calabi-Yau manifold while maintaining a
Minkowski vacuum. Certain deformations of the Calabi-Yau complex structure,
with all other moduli held fixed, can lead to the gauge bundle becoming
non-holomorphic and, hence, non-supersymmetric. This leads to an F-term
potential which stabilizes the corresponding complex structure moduli. We use
10- and 4-dimensional field theory arguments as well as a derivation based
purely on algebraic geometry to show that this picture is indeed correct. An
explicit example is presented in which a large subset of complex structure
moduli is fixed. We demonstrate that this type of theory can serve as the
hidden sector in heterotic vacua and can co-exist with realistic particle
physics.Comment: 17 pages, Late
Numerical Hermitian Yang-Mills Connections and Vector Bundle Stability in Heterotic Theories
A numerical algorithm is presented for explicitly computing the gauge
connection on slope-stable holomorphic vector bundles on Calabi-Yau manifolds.
To illustrate this algorithm, we calculate the connections on stable monad
bundles defined on the K3 twofold and Quintic threefold. An error measure is
introduced to determine how closely our algorithmic connection approximates a
solution to the Hermitian Yang-Mills equations. We then extend our results by
investigating the behavior of non slope-stable bundles. In a variety of
examples, it is shown that the failure of these bundles to satisfy the
Hermitian Yang-Mills equations, including field-strength singularities, can be
accurately reproduced numerically. These results make it possible to
numerically determine whether or not a vector bundle is slope-stable, thus
providing an important new tool in the exploration of heterotic vacua.Comment: 52 pages, 15 figures. LaTex formatting of figures corrected in
version 2
Means and covariance functions for geostatistical compositional data: an axiomatic approach
This work focuses on the characterization of the central tendency of a sample
of compositional data. It provides new results about theoretical properties of
means and covariance functions for compositional data, with an axiomatic
perspective. Original results that shed new light on the geostatistical
modeling of compositional data are presented. As a first result, it is shown
that the weighted arithmetic mean is the only central tendency characteristic
satisfying a small set of axioms, namely continuity, reflexivity and marginal
stability. Moreover, this set of axioms also implies that the weights must be
identical for all parts of the composition. This result has deep consequences
on the spatial multivariate covariance modeling of compositional data. In a
geostatistical setting, it is shown as a second result that the proportional
model of covariance functions (i.e., the product of a covariance matrix and a
single correlation function) is the only model that provides identical kriging
weights for all components of the compositional data. As a consequence of these
two results, the proportional model of covariance function is the only
covariance model compatible with reflexivity and marginal stability
Fetal exome sequencing for isolated increased nuchal translucency: should we be doing it?
Objective:
To evaluate the utility of prenatal exome sequencing (ES) for isolated increased nuchal translucency (NT) and investigate factors which increase diagnostic yield.
Design:
Retrospective analysis of data from two prospective cohort studies.
Setting:
Fetal medicine centres in the UK and USA.
Population:
Fetuses with increased NT ≥3.5mm at 11-14 weeks’ gestation recruited to the Prenatal Assessment of Genomes and Exomes (PAGE) and Columbia fetal WES studies (n = 213).
Methods:
We grouped cases based on (i) the presence of additional structural abnormalities at presentation in the first trimester or later in pregnancy, and (ii) NT measurement at presentation. We compared diagnostic rates between groups using Fisher exact test.
Main Outcome Measures:
Detection of diagnostic genetic variants considered to have caused the observed fetal structural anomaly.
Results:
Diagnostic variants were detected in 12 (22.2%) of 54 fetuses presenting with non-isolated increased NT, 12 (32.4%) of 37 fetuses with isolated increased NT in the first trimester and additional abnormalities later in pregnancy, and 2 (1.8%) of 111 fetuses with isolated increased NT in the first trimester and no other abnormalities on subsequent scans. Diagnostic rate also increased with increasing size of NT.
Conclusions:
The diagnostic yield of prenatal ES is low for fetuses with isolated increased NT but significantly higher where there are additional structural anomalies. Prenatal ES may not be appropriate for truly isolated increased NT but timely, careful ultrasound scanning to identify other anomalies emerging later can direct testing to focus where there is a higher likelihood of diagnosis
B-L Cosmic Strings in Heterotic Standard Models
E_{8} X E_{8} heterotic string and M-theory, when compactified on smooth
Calabi-Yau manifolds with SU(4) vector bundles, can give rise to softly broken
N=1 supersymmetric theories with the exact matter spectrum of the MSSM,
including three right-handed neutrinos and one Higgs-Higgs conjugate pair of
supermultiplets. These vacua have the SU(3)_{C} X SU(2)_{L} X U(1)_{Y} gauge
group of the standard model augmented by an additional gauged U(1)_{B-L}. Their
minimal content requires that the B-L symmetry be spontaneously broken by a
vacuum expectation value of at least one right-handed sneutrino. The soft
supersymmetry breaking operators can induce radiative breaking of the B-L gauge
symmetry with an acceptable B-L/electroweak hierarchy. In this paper, it is
shown that U(1)_{B-L} cosmic strings occur in this context, potentially with
both bosonic and fermionic superconductivity. We present a numerical analysis
that demonstrates that boson condensates can, in principle, form for theories
of this type. However, the weak Yukawa and gauge couplings of the right-handed
sneutrino suggests that bosonic superconductivity will not occur in the
simplest vacua in this context. The electroweak phase transition also disallows
fermion superconductivity, although substantial bound state fermion currents
can exist.Comment: 41 pages, 5 figure
Flavor Structure in F-theory Compactifications
F-theory is one of frameworks in string theory where supersymmetric grand
unification is accommodated, and all the Yukawa couplings and Majorana masses
of right-handed neutrinos are generated. Yukawa couplings of charged fermions
are generated at codimension-3 singularities, and a contribution from a given
singularity point is known to be approximately rank 1. Thus, the approximate
rank of Yukawa matrices in low-energy effective theory of generic F-theory
compactifications are minimum of either the number of generations N_gen = 3 or
the number of singularity points of certain types. If there is a geometry with
only one E_6 type point and one D_6 type point over the entire 7-brane for
SU(5) gauge fields, F-theory compactified on such a geometry would reproduce
approximately rank-1 Yukawa matrices in the real world. We found, however, that
there is no such geometry. Thus, it is a problem how to generate hierarchical
Yukawa eigenvalues in F-theory compactifications. A solution in the literature
so far is to take an appropriate factorization limit. In this article, we
propose an alternative solution to the hierarchical structure problem (which
requires to tune some parameters) by studying how zero mode wavefunctions
depend on complex structure moduli. In this solution, the N_gen x N_gen CKM
matrix is predicted to have only N_gen entries of order unity without an extra
tuning of parameters, and the lepton flavor anarchy is predicted for the lepton
mixing matrix. We also obtained a precise description of zero mode
wavefunctions near the E_6 type singularity points, where the up-type Yukawa
couplings are generated.Comment: 148 page
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